[Show abstract][Hide abstract] ABSTRACT: Applying proper coding is important for doctors practicing gastroenterology. The coding systems established by various organizations define tumors differently. As a result of changing concepts of tumor classification, there are coding and reimbursement issues following the confirmation of malignant lesions by nationwide cancer screening in patients with intramucosal carcinoma and neuroendocrine tumors of the colorectum. In addition, there have been discrepancies between the views of endoscopists and pathologists regarding tumor coding. The Korean Society of Gastrointestinal Endoscopy held an expert meeting and established a consensus for the coding of intramucosal carcinoma and neuroendocrine tumor of the colorectum.
[Show abstract][Hide abstract] ABSTRACT: In 2010, the World Health Organization (WHO) categorized L-cell type neuroendocrine tumors (NETs) as tumors of uncertain malignancy, while all others were classified as malignant. However, the diagnostic necessity of L-cell immunophenotyping is unclear, as are tumor stage and grade that may guide diagnosis and management. To clarify the predictive markers of rectal neuroendocrine neoplasms (NENs), 5- and 10-year overall survival (OS) was analyzed by pathological parameters includingL-cell phenotype. Material and methods A total of 2385 rectal NENs were analyzed from our previous multicenter study and a subset of 170 rectal NENs was immunophenotyped.
In univariate survival analysis, tumor grade (p<0.0001), extent (p<0.0001), size (p<0.0001), lymph node metastasis (p=0.0063), and L cell phenotype (p<0.0001) showed significant correlation with the prognosis of rectal NENs; however, none of these markers achieved independent significance in multivariate analysis. The 10-year-OS of tumors of NET grade1, <10mm, the mucosa/submucosawas 97.58%, 99.47%, and 99.03%, respectively. L-cell marker, glucagon II (GLP-1&2),with a cut off score of >10, is useful in defining L-cell type. In this study, an L-cell immunophenotype was found in 83.5% of all rectal NENs and most, but not all L-cell type tumors were NET G1, small (<10mm) and confined to the mucosa/submucosa.
From these results, the biological behavior of rectal NENs does not appear to be determined by L-cell type alone but instead by a combination of pathological parameters.
Cancer Research and Treatment 02/2015; DOI:10.4143/crt.2014.238 · 2.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Inevitable loss of diagnostic material should be minimized during cell block preparation. We introduce a modified agarose cell block technique that enables the synthesis of compact cell blocks by using the entirety of a cell pellet without the loss of diagnostic material during cell block preparations. The feasibility of this technique is illustrated by high-throughput immunocytochemistry using high-density cell block microarray (CMA).
The cell pellets of Sure- Path residues were pre-embedded in ultra-low gelling temperature agarose gel and re-embedded in standard agarose gel. They were fixed, processed, and embedded in paraffin using the same method as tissue sample processing. The resulting agarose cell blocks were trimmed and represented on a CMA for high-throughput analysis using immunocytochemical staining.
The SurePath residues were effectively and entirely incorporated into compact agarose cell buttons and embedded in paraffin. Sections of the agarose cell blocks revealed cellularities that correlated well with corresponding SurePath smears and had immunocytochemical features that were sufficient for diagnosis of difficult cases.
This agarose-based compact cell block technique enables preparation of high-quality cell blocks by using up the residual SurePath samples without loss of diagnostic material during cell block preparation.
The Korean Journal of Pathology 10/2014; 48(5):351-60. DOI:10.4132/KoreanJPathol.2014.48.5.351 · 0.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Epithelial mesenchymal transition (EMT) has an important role in invasion and metastasis of tumor cells. The purpose of this study was to evaluate the roles of EMT-associated proteins on progression and metastasis as a prognostic/predictive factor in curatively-resected (R0) head and neck squamous cell carcinoma (HNSCC).
A total of 118 patients who received curative surgery for HNSCC at Inha University Hospital between January 1996 and December 2011 were included. We used protein immunohistochemistry to evaluate the expression of E-cadherin, vimentin, and EZH2 on tissue microarrays. Also, we reviewed all medical records and analyzed the relationship between the expression of EMT-associated proteins and prognosis.
The E-cadherin-negative group showed more moderate/poor differentiation of cancer cell type than the higher E-cadherin-expressing group (p=.016) and high EZH2 expression was significantly correlated with nodal metastasis (p=.012). Our results demonstrate a significant association between high expression of EZH2 and vimentin and presence of distant progression (p=.026). However, expression of E-cadherin, vimentin, and EZH2 was not significantly associated with overall survival.
These findings suggest that an EMT-associated protein expression profile is correlated with aggressiveness of disease and prognosis, and could be a useful marker for determination of additional treatment in curatively-resected HNSCC patients.
The Korean Journal of Pathology 08/2014; 48(4):263-9. DOI:10.4132/KoreanJPathol.2014.48.4.263 · 0.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Photodynamic therapy (PDT) is a new therapeutic approach for the palliative treatment of malignant bile duct obstruction. In this study, we designed photosensitizer-embedded self-expanding nonvascular metal stent (PDT-stent) which allows repeatable photodynamic treatment of cholangiocarcinoma without systemic injection of photosensitizer. Polymeric photosensitizer (pullulan acetate-conjugated pheophorbide A; PPA) was incorporated in self-expanding nonvascular metal stent. Residence of PPA in the stent was estimated in buffer solution and subcutaneous implantation on mouse. Photodynamic activity of PDT-stent was evaluated through laserexposure on stent-layered tumor cell lines, HCT-116 tumor-xenograft mouse models and endoscopic intervention of PDT-stent on bile duct of mini pigs. Photo-fluorescence imaging of the PDT-stent demonstrated homogeneous embedding of polymeric Pheo-A (PPA) on stent membrane. PDT-stent sustained its photodynamic activities at least for 2 month. And which implies repeatable endoscopic PDT is possible after stent emplacement. The PDT-stent after light exposure successfully generated cytotoxic singlet oxygen in the surrounding tissues, inducing apoptotic degradation of tumor cells and regression of xenograft tumors on mouse models. Endoscopic biliary in-stent photodynamic treatments on minipigs also suggested the potential efficacy of PDT-stent on cholangiocarcinoma. In vivo and in vitro studies revealed our PDT-stent, allows repeatable endoscopic biliary PDT, has the potential for the combination therapy (stent plus PDT) of cholangiocarcinoma.
[Show abstract][Hide abstract] ABSTRACT: Although, gastric cancer is quite common in Korea, the treatment outcome is relatively favorable compared to that of Western countries. However, there is no Korean multidisciplinary guideline for gastric cancer and thus, a guideline adequate for domestic circumstances is required. Experts from related societies developed 22 recommendation statements for the diagnosis (n=9) and treatment (n=13) based on relevant key questions. Evidence levels based on systematic review of literatures were classified as five levels from A to E, and recommendation grades were classified as either strong or weak. The topics of this guideline cover diagnostic modalities (endoscopy, endoscopic ultrasound, radiologic diagnosis), treatment modalities (surgery, therapeutic endoscopy, chemotherapy, radiotherapy) and pathologic evaluation. External review of the guideline was conducted at the finalization phase. (Korean J Gastroenterol 2014;63:66-81).
The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi 02/2014; 63(2):66-81. DOI:10.5230/jgc.2014.14.2.87
[Show abstract][Hide abstract] ABSTRACT: Hepatitis B virus (HBV) replication detected before the resection of hepatocellular carcinoma (HCC) is to be controlled by antiviral agents. However, management strategy for patients with preoperatively undetectable HBV DNA without antiviral therapy is not clearly delineated. This study investigated viral reactivation after the liver resection in non-replicating HBV DNA related HCC patients and its impact on the surgical outcome.
From 198 patients that underwent liver resection due to HBV related HCC, 101 patients who had serially checked serum HBV DNA were analyzed.
From 101 patients, 33 patients had baseline undetectable HBV DNA. Eleven patients (11/33, 33.3%) had viral replication after the liver resection. The postoperative viral reactivation (HR: 2.144; 95% CI: 1.122-4.097; p=0.021), along with existence of satellite nodules (HR: 3.034; 95% CI: 1.1.376-6.689; p=0.006), existence of microvascular invasion (HR: 2.479; 95% CI: 1.303-4.718; p=0.006), and HBeAg positivity (HR: 2.059; 95% CI: 1.155-3.670; p=0.014) predicted recurrence after the surgery. Quantification of intrahepatic total and covalently closed circular DNA (cccDNA) was done in 14 patients whose baseline serum HBV DNA was undetectable without the use of antiviral agent. Amount of intrahepatic cccDNA expressed as copies/hepatocyte in patients with postoperative viral reactivation showed significantly higher than those in patients with sustained negative serum HBV DNA (p=0.010).
This study shows that naturally suppressed preoperative HBV without application of antiviral agent does not ensure undetectable serum HBV after the surgery, and postoperative viral reactivation might be associated with HCC recurrence.
Journal of Gastroenterology and Hepatology 12/2013; 29(5). DOI:10.1111/jgh.12472 · 3.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Self-made tissue punches can be effectively used to punch holes in blank recipient paraffin blocks and extract tissue cores from the donor paraffin blocks for the low-cost construction of tissue microarrays (TMAs). However, variable degrees of section distortion and loss of the tissue cores can occurs during cutting of the TMAs, posing technical problems for in-house manual construction of high-density TMAs. We aimed to update the method for in-house manual TMA construction to improve the quality of high-density TMAs.
Blocks of agarose gel were subjected to the standard tissue processing and embedding procedure to prepare recipient agarose-paraffin blocks. The self-made tissue punches and recipient agarose-paraffin blocks were used to construct TMAs, which were completely melted and re-embedded in paraffin to make finished TMA blocks.
The donor tissue cores were completely integrated into the surrounding paraffin of the recipient blocks. This method enabled us to construct high-density TMAs with significantly less section distortion or loss of tissue cores during microtomy.
Simple and inexpensive construction of high-density and high-quality TMAs can be warranted by using paraffinized agarose gels as recipient blocks.
The Korean Journal of Pathology 06/2013; 47(3):238-44. DOI:10.4132/KoreanJPathol.2013.47.3.238 · 0.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There is confusion in the diagnosis and biological behaviors of gastroenteropancreatic neuroendocrine tumors (GEP-NETs), because of independently proposed nomenclatures and classifications. A standardized form of pathology report is required for the proper management of patients.
We discussed the proper pathological evaluation of GEP-NET at the consensus conference of the subcommittee meeting for the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. We then verified the prognostic significance of pathological parameters from our previous nationwide collection of pathological data from 28 hospitals in Korea to determine the essential data set for a pathology report.
Histological classification, grading (mitosis and/or Ki-67 labeling index), T staging (extent, size), lymph node metastasis, and lymphovascular and perineural invasion were significant prognostic factors and essential for the pathology report of GEP-NET, while immunostaining such as synaptophysin and chromogranin may be optional. Furthermore, the staging system, either that of the 2010 American Joint Cancer Committee (AJCC) or the European Neuroendocrine Tumor Society (ENETS), should be specified, especially for pancreatic neuroendocrine neoplasms.
A standardized pathology report is crucial for the proper management and prediction of prognosis of patients with GEP-NET.
The Korean Journal of Pathology 06/2013; 47(3):227-37. DOI:10.4132/KoreanJPathol.2013.47.3.227 · 0.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The incidence of early colorectal epithelial neoplasm (ECEN) is increasing, and its pathologic diagnosis is important for patient care. We investigated the incidence of ECEN and the current status of its pathologic diagnosis.
We collected datasheets from 25 institutes in Korea for the incidence of colorectal adenoma with high grade dysplasia (HGD) and low grade dysplasia in years 2005, 2007, and 2009; and early colorectal carcinoma in the year 2009. We also surveyed the diagnostic terminology of ECEN currently used by the participating pathologists.
The average percentage of diagnoses of adenoma HGD was 7.0%, 5.0%, and 3.4% in years 2005, 2007, and 2009, respectively. The range of incidence rates of adenoma HGD across the participating institutes has gradually narrowed over the years 2005 to 2009. The incidence rate of early colorectal carcinoma in the year 2009 was 21.2%. The participants did not share a single criterion or terminology for the diagnosis of adenoma HGD. The majority accepted the diagnostic terms that distinguished noninvasive, mucosal confined, and submucosal invasive carcinoma.
Further research requirements suggested are a diagnostic consensus for the histopathologic diagnosis of ECEN; and standardization of diagnostic terminology critical for determining the disease code.
The Korean Journal of Pathology 06/2013; 47(3):245-51. DOI:10.4132/KoreanJPathol.2013.47.3.245 · 0.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Small intestinal adenocarcinomas (SIACs) are rare, and their molecular pathogenesis is largely unknown. To define the roles of E-cadherin and β-catenin, we performed immunohistochemistry for E-cadherin and β-catenin in 194 surgically resected SIACs with tissue microarrays and compared the data with clinicopathologic factors, including survival rates of patients with SIAC. Loss of E-cadherin expression and aberrant β-catenin expression were observed in 41.8% (81/194 cases) and 40.7% (79/194 cases) of SIACs, respectively. Combined loss of E-cadherin and aberrant β-catenin expression was observed in 24.2% (47/194 cases) of SIACs, and this feature was most frequently observed in mucinous adenocarcinomas and signet ring cell carcinomas (P < .001), poorly differentiated and undifferentiated carcinomas (P < .001), and tumors with advanced pT classification (P = .03). Survival times for patients with SIAC with both loss of E-cadherin and aberrant β-catenin expression (median, 13.9 months) were significantly shorter than those for patients without aberrant expression of both proteins (49.9 months), as determined by univariate (P < .001) and multivariate (P = .01) analyses. In conclusion, loss of E-cadherin and aberrant β-catenin expression correlate with poorly differentiated tumors, advanced T classification, and decreased patient survival time; therefore, it could be a prognostic factor in patients with SIAC.
American Journal of Clinical Pathology 02/2013; 139(2):167-76. DOI:10.1309/AJCPS54RTFCTHGWX · 3.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A case of peripheral primitive neuroectodermal tumor of the small bowel mesentery with osseous component is reported. A 23-year-old man was admitted to our hospital because of acute severe abdominal pain. Abdominal computed tomography revealed a large solid and cystic, oval shaped mass, measuring 11.0×6.0 cm in the pelvic cavity. Histologically the resected lesion consisted of sheets of undifferentiated small round cells forming Homer-Wright rosettes and perivascular pseudorosettes, and showed areas of osteoid and bone formation. Immunohistochemical studies revealed that tumor cells expressed positivity against CD99 (MIC2), CD57, neuron-specific enolase, and vimentin. Fluorescence in situ hybridization study revealed Ewing sarcoma breakpoint region 1 (EWSR1) gene rearrangement on chromosome 22q12. To the authors' knowledge this is the first documentation of a peripheral neuroectodermal tumor with osteoid and bone formation of the small bowel mesentery.
The Korean Journal of Pathology 02/2013; 47(1):77-81. DOI:10.4132/KoreanJPathol.2013.47.1.77 · 0.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Laparoscopic Heller myotomy with antireflux procedure is considered to be a standard treatment for achalasia. Recently, peroral endoscopic myotomy (POEM) was developed and performed on patients with achalasia. However, there is no report on POEM use in South Korea. The aim of this study was to evaluate the technical feasibility of POEM in a porcine model.
POEM was performed on two mini pigs. We performed upper endoscopy under general anesthesia. A submucosal tunnel was created and the circular muscle layer was incised using several knives. The mucosal entry was closed using resolution clips. We performed a follow-up endoscopy and sacrificed the pigs 2 weeks after the POEM. The myotomy site was evaluated grossly and histologically.
POEM was successfully performed on the two mini pigs. No injuries to any abdominal or mediastinal structures occurred. Two weeks after the POEM, the esophageal mucosa healed without any endoscopic evidence of complications. Necropsy revealed that the circular muscle layer was completely lost and replaced with fibrotic tissue.
We found that POEM is a technically feasible method which can be performed on an animal model. However, to ensure safe use on patients with achalasia, further studies on technical methods and long-term follow-up examinations are required.
[Show abstract][Hide abstract] ABSTRACT: Cytomegalovirus (CMV) infection has been described in immunosuppressed individuals such as patients with AIDS, those receiving chemotherapy, and post-transplantation. CMV can cause severe disease either via reactivation of latent virus or via primary infection. In immunocompetent patients, CMV infection is usually transient and does not exhibit many symptoms. The colon is the site most frequently affected by severe CMV disease in immunocompetent patients. Clinically, CMV colitis commonly presents with diarrhea, fever, and abdominal pain. Although some patients recover spontaneously, others suffer from severe complications, such as bowel perforation, severe gastrointestinal bleeding and, rarely, stricture, and surgery is the choice of treatment in these patients. We report a case of stricture of the proximal transverse colon, presenting as a complication of CMV colitis, in an immunocompetent man with acute respiratory distress syndrome. We performed laparoscopic segmental resection of the proximal transverse colon.
[Show abstract][Hide abstract] ABSTRACT: Background: A metabolomic study of biomarkers associated with dimethylnitrosamine (DMN)-induced hepatic fibrosis in Sprague-Dawley rats was performed using GC-MS. The clinical chemistry of the collected blood and the histopathology of excised liver samples were examined, and urine samples were prepared by solvent extraction. Results: Through pattern analysis, the DMN-treated group was divided into two subgroups based on the aspartate aminotransferase (AST) levels compared with the control, a moderately higher group (DMN subgroup A) and a significantly higher group (DMN subgroup B). Uric acid, orotic acid, N-phenylacetylglycine and glutaric acid were biomarkers for DMN subgroup A, aminomalonic acid was a biomarker for DMN subgroup B, and arabitol level distinguished control versus DMN treatment regardless of AST level. Conclusion: This study suggests that the identification and profiling of AST level-related metabolites may be useful as a diagnostic tool and for the study of the mechanism of liver fibrosis induced by DMN.
[Show abstract][Hide abstract] ABSTRACT: Dietary restriction (DR) has many beneficial effects, but the detailed metabolic mechanism remains largely unresolved. As diet is essentially related to metabolism, we investigated the metabolite profiles of urines from control and DR animals using NMR and LC-Mass metabolomic approaches. Multivariate analysis presented distinctive metabolic profiles and marker signals from glucuronide and glycine conjugations pathways in the DR group. Broad profiling of the urine phase II metabolites with neutral loss scanning showed that glucuronide and glycine conjugation metabolites are generally higher in the DR group. The up-regulation of the phase II detoxifications in the DR group were confirmed by mRNA and protein expression levels of the UGT's and GLYAT's in actual liver tissues. Histopathology and serum biochemistry showed that the DR had beneficial effects of low serum ALT level and low glycogen granules in liver. In addition, the Nrf-2 signaling pathway was shown to be up-regulated, providing a mechanistic clue for the enhanced phase II detoxification in liver tissue. Taken together, our metabolomic and biochemical studies provide a possible metabolic perspective in understanding the complex mechanism of the beneficial effects of DR.
[Show abstract][Hide abstract] ABSTRACT: Advances of tissue microarray (TMA) technology have enabled simultaneous in situ analysis of biomarker expression in a large number of archived pathology specimens. However, the relatively high cost of TMA construction may hamper many researchers from using this essential tool of modern pathology research. We discuss methods for making TMA kits and recipient blocks for manual construction of high-density TMAs at low cost.
Ordinary cannula piercing needles, hypodermic needles, bone marrow biopsy needles, metallic ink cartridges of ballpoint pens, and disposable skin biopsy punches were used to construct self-made manual TMA kits. The recipient blocks were manufactured by boring holes in the conventional bare paraffin blocks. A mini electric hand drill and a microcompound table assembled on a drill stand were used to maximize the capacity of the recipient blocks.
By using TMA kits made from cannula piercing needles (16- and 18-gauge), it was possible to construct TMAs with 1 mm×140 cores, 0.6 mm×320 cores, 2 mm×70 cores, 3 mm×35 cores, and 5 mm×12 cores. The capacity of the recipient blocks could be dramatically increased by drilling holes.
Construction of TMAs using self-made TMA kits is an inexpensive alternative to construction of TMAs using commercial devices.
The Korean Journal of Pathology 12/2012; 46(6):562-8. DOI:10.4132/KoreanJPathol.2012.46.6.562 · 0.17 Impact Factor